Cisplatin‐resistant osteosarcoma cell‐derived exosomes confer cisplatin resistance to recipient cells in an exosomal circ_103801‐dependent manner

Abstract

Studies have shown that exosomes can mediate the chemoresistance of drug‐resistant cells by transmitting circular RNAs (circRNAs). However, the role of exosome‐derived hsa_circ_103801 (exosomal hsa_circ_103801) in osteosarcoma (OS) remains unclear. The level of hsa_circ_103801 was upregulated in the serum exosomes from patients with OS, and OS patients with high hsa_circRNA_103801 expression had a shorter survival time relative to patients with low hsa_circ_103801 expression. The expression of hsa_circ_103801 was upregulated in cisplatin‐resistant MG63 (MG63/CDDP) cells compared with that in MG63 cells. In addition, hsa_circ_103801 was highly enriched in exosomes derived from CDDP‐resistant OS cells and could be delivered to MG63 and U2OS cells through exosomes. Exosomes derived from CDDP‐resistant cells were shown to reduce the sensitivity of MG63 and U2OS cells to CDDP, inhibit apoptosis, and increase the expression of multidrug resistance‐associated protein 1 and P‐glycoprotein. Moreover, exosomal hsa_circ_103801 could strengthen the promotive effect of exosomes on the chemoresistance of MG63 and U2OS cells to CDDP. Hence, serum exosomal hsa_circ_103801 may serve as an effective prognostic biomarker for OS, and exosomal hsa_circ_103801 could be a potential target for overcoming OS chemoresistance.

Recent advances in the contribution of circRNAs to cisplatin chemotherapy resistance in cancers

“…Exosome-mediated circRNAs transfer is another mechanism of CDDP resistance of OS. Pan et al [63] found hsa_circ_103801 was significantly higher in the serum exosomes from OS patients than that in the serum exosomes from healthy controls. The higher expression of hsa_circ_103801 in serum exosomal was correlated with shorter survival in OS patients.…”

The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

“…Pan et al showed that exosomes from cisplatinresistant cells (CDDP) reduced the sensitivity of MG63 and U2OS cells to CDDP, inhibited cell apoptosis, and increased the levels of multidrug resistance-related protein 1 and P-glycoprotein expression [87]. In addition, exosomal hsa_circ_103801 could enhance the promoter function of exosomes and promote the chemoresistance of MG63 and U2OS cells to CDDP [87]. Wei et al found that the prepared doxorubicin-loaded exosomes could be used as an excellent chemotherapeutic drug for the treatment of osteosarcoma in vitro [88].…”

The Significance of Exosomes in Pathogenesis, Diagnosis, and Treatment of Esophageal Cancer

“…Studies have confirmed that the level of circRNAs was significantly enriched in exosomes compared to exosome-derived cells. 75 The circRNAs also play a critical role in the progression of ESCC. Fan et al validated circRNA has-circ-0001946 and has-circ-0043603 secreted by ESCC cells might be potential diagnostic biomarkers for ESCC.…”